ArticleMarine drugs2014
The marine-derived sipholenol A-4-O-3',4'-dichlorobenzoate inhibits breast cancer growth and motility in vitro and in vivo through the suppression of Brk and FAK signaling.
Article in Marine drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors.Marine drugs · 2019Pooled it
- Demethylmycemycin A, a dibenzoxazepinone from the marine-derived Dactylosporangium sp. OK1079, with prostate cancer suppressive effects via targeting BRK-FAK-STAT3 axis.The Journal of antibiotics · 2026Article
- Targeting Focal Adhesion Kinase in Lung Diseases: Current Progress and Future Directions.Biomolecules · 2025Review
- The Suppression of Signal Transducer and Activator of Transcription-3 in A549 human Lung Carcinoma Cells Induced by Marine SpongeJournal of experimental pharmacology · 2025Article
- FAK inhibitors as promising anticancer targets: present and future directions.Future medicinal chemistry · 2021Review
- Collective Locomotion of Human Cells, Wound Healing and Their Control by Extracts and Isolated Compounds from Marine Invertebrates.Molecules (Basel, Switzerland) · 2020Review
- High resolution crystal structure of the FAK FERM domain reveals new insights on the Druggability of tyrosine 397 and the Src SH3 binding site.BMC molecular and cell biology · 2019Article
- Marine Natural Products as Models to Circumvent Multidrug Resistance.Molecules (Basel, Switzerland) · 2016Review
- Chemical Diversity and Biological Properties of Secondary Metabolites from Sea Hares of Aplysia Genus.Marine drugs · 2016Review
- Molecular architecture and biomedical leads of terpenes from red sea marine invertebrates.Marine drugs · 2015Review
- Araguspongine C induces autophagic death in breast cancer cells through suppression of c-Met and HER2 receptor tyrosine kinase signaling.Marine drugs · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Sipholenol A is a natural sipholane triterpenoid isolated from the Red Sea sponge, Callyspongia siphonella. Previous studies showed the antimigratory and antiproliferative activities of the semisynthetic sipholenol A esters against breast cancer cell lines. This study investigated the effects of sipholenol A-4-O-3',4'-dichlorobenzoate (SPA) on the growth, migration and invasion of diverse human breast cancer cells. Results showed that SPA inhibited the growth of the human breast cancer cells, MDA-MB-231, MCF-7, BT-474 and T-47D, in a dose-dependent manner. Immunofluorescent analysis showed that SPA significantly reduced Ki-67-positive cells in MDA-MB-231 cells. Flow cytometry and Western blot analyses revealed that SPA treatment suppressed MDA-MB-231 cell growth by inducing cell cycle arrest at the G1 phase. In addition, SPA suppressed breast cancer cell migration, invasion and decreased Brk and FAK activation in a dose-dependent manner. Molecular docking study suggested a perfect fitting at the FAK's FERM domain, inhibiting the main autophosphorylation site, Y397, which was further confirmed by Western blot analysis. Most known small molecule FAK inhibitors target the kinase domain, creating several off-target side effects. The in vivo studies showed that SPA treatment suppressed breast tumor growth and Ki-67, CD31, p-Brk and p-FAK expression in orthotopic breast cancer in nude mice. In conclusion, SPA inhibited the growth, invasion and migration of breast cancer cells possibly via deactivating Brk and FAK signaling, suggesting good potential for therapeutic use to control invasive breast cancer.
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